Article abstract
Nature Immunology 9, 1270 - 1278 (2008)
Published online: 5 October 2008 | doi:10.1038/ni.1661
CEACAM1 inhibits Toll-like receptor 2–triggered antibacterial responses of human pulmonary epithelial cells
Hortense Slevogt1, Solveig Zabel1, Bastian Opitz1, Andreas Hocke1, Julia Eitel1, Philippe D N'Guessan1, Lothar Lucka2, Kristian Riesbeck3, Wolfgang Zimmermann4, Janine Zweigner5, Bettina Temmesfeld-Wollbrueck1, Norbert Suttorp1 & Bernhard B Singer2,6
Abstract
Although Moraxella catarrhalis and Neisseria meningitidis are important human pathogens, they often colonize the human respiratory tract without causing overt clinical symptoms. Both pathogens express structurally unrelated proteins that share the ability to stimulate the adhesion molecule CEACAM1 expressed on human cells. Here we demonstrate that the interaction of CEACAM1 with ubiquitous surface protein A1 expressed on M. catarrhalis or with opacity-associated proteins on N. meningitidis resulted in reduced Toll-like receptor 2–initiated transcription factor NF-
B–dependent inflammatory responses of primary pulmonary epithelial cells. These inhibitory effects were mediated by tyrosine phosphorylation of the immunoreceptor tyrosine-based inhibitory motif of CEACAM1 and by recruitment of the phosphatase SHP-1, which negatively regulated Toll-like receptor 2–dependent activation of the phosphatidylinositol 3-OH kinase–Akt kinase pathway. Our results identify a CEACAM1-dependent immune-evasion strategy.
- Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany.
- Institute for Biochemistry and Molecular Biology, Charité-Universitätsmedizin Berlin, 14195 Berlin, Germany.
- Department of Medical Microbiology, Malmö University Hospital, Lund University, SE-205 02 Malmö, Sweden.
- Tumor Immunology Laboratory, Ludwig-Maximilians-University, University Hospital-Grosshadern, D-81377 Munich, Germany.
- Department of Microbiology and Hygiene, Charité-Universitätsmedizin Berlin, 12203 Berlin, Germany.
- Institute of Anatomy, University Hospital Essen, 45147 Essen, Germany.
Correspondence to: Hortense Slevogt1 e-mail: hortense.slevogt@charite.de
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